Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90.
The 90-kDa heat shock protein (HSP90) is a molecular chaperone that assists in the folding and assembly of proteins in the cytosol. We previously demonstrated that the antineoplastic reagent, cisplatin, inhibits the aggregation prevention activity of mammalian HSP90. We now show that cisplatin binds both the amino terminal and carboxyl terminal domains of the human HSP90 and differently affects these two domains. Cisplatin blocks the aggregation prevention activity of HSP90C, but not HSP90N. In contrast, cisplatin induces a conformational change in HSP90N, but not HSP90C. These results indicate that cisplatin modulates the HSP90 activities through two different mechanisms using the two distinct binding sites of the HSP90 molecule.
Ishida
Ryuichi
R
Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan.
Takaoka
Yuka
Y
Yamamoto
Soh
S
Miyazaki
Toshio
T
Otaka
Michiro
M
Watanabe
Sumio
S
Komatsuda
Atushi
A
Wakui
Hideki
H
Sawada
Ken-Ichi
K
Kubota
Hiroshi
H
Itoh
Hideaki
H
D020816:Amino Acid Motifs; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D017434:Protein Structure, Tertiary / Q000187:drug effects
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D002945:Cisplatin